Cormagnesin^® (Solution) Instructions for Use

ATC Code

B05XA05 (Magnesium sulphate)

Active Substance

Magnesium sulphate (Ph.Eur. European Pharmacopoeia)

Clinical-Pharmacological Group

Magnesium preparation

Pharmacotherapeutic Group

Vasodilating agent

Pharmacological Action

When taken orally, it exerts a choleretic (reflex action on the receptors of the duodenal mucosa) and a laxative effect (due to the poor absorption of magnesium sulphate in the intestine, high osmotic pressure is created, water accumulates in the intestine, the intestinal contents are liquefied, and peristalsis is enhanced). It is an antidote in cases of poisoning by heavy metal salts. The onset of effect is within 0.5-3 hours, duration is 4-6 hours.

When administered parenterally, it exerts hypotensive, sedative, and anticonvulsant effects, as well as diuretic, arteriodilating, antiarrhythmic, vasodilating (on arteries) action; in high doses, it has a curare-like effect (depressing influence on neuromuscular transmission), tocolytic, hypnotic, and narcotic action, and suppresses the respiratory center. Magnesium is a physiological blocker of slow calcium channels and is capable of displacing it from binding sites. It regulates metabolic processes, interneuronal transmission, and muscle excitability, prevents the entry of calcium through the presynaptic membrane, reduces the amount of acetylcholine in the peripheral nervous system and CNS. It relaxes smooth muscles, lowers blood pressure (primarily elevated), and enhances diuresis.

The mechanism of the anticonvulsant action is associated with a reduction in the release of acetylcholine from neuromuscular synapses, whereby magnesium suppresses neuromuscular transmission and exerts a direct depressant effect on the CNS.

The antiarrhythmic action of magnesium is due to a decrease in the excitability of cardiomyocytes, restoration of ionic equilibrium, stabilization of cell membranes, and impairment of sodium current, slow inward calcium current, and unidirectional potassium current. The cardioprotective effect is due to the dilation of coronary arteries, reduction of total peripheral vascular resistance and platelet aggregation.

The tocolytic action develops as a result of inhibition of myometrial contractility (reduction in the uptake, binding, and distribution of calcium in smooth muscle cells) under the influence of magnesium ions, and enhancement of uterine blood flow due to the dilation of its vessels. Magnesium is an antidote in cases of poisoning by heavy metal salts.

Systemic effects develop almost instantly after IV administration and after 1 hour after IM administration. The duration of action after IV administration is 30 minutes, after IM administration it is 3-4 hours.

Pharmacokinetics

After oral administration, no more than 20% of the administered dose is absorbed.

The steady-state concentration (C_ss) at which the anticonvulsant effect develops is 2-3.5 mmol/L.

It crosses the blood-brain barrier and the placental barrier, and is excreted in breast milk at a concentration twice that in plasma. It is eliminated by the kidneys, the rate of renal excretion is proportional to the plasma concentration and the level of glomerular filtration.

Indications

For oral administration: constipation, cholangitis, cholecystitis, gallbladder dyskinesia of the hypotonic type (for tubage), duodenal intubation (to obtain the cystic portion of bile), bowel cleansing before diagnostic procedures.

For parenteral administration: arterial hypertension (including hypertensive crisis with signs of cerebral edema), hypomagnesemia (including increased magnesium requirement and acute hypomagnesemia – tetany, impaired myocardial function), polymorphic ventricular tachycardia (torsades de pointes type), urinary retention, encephalopathy, epileptic syndrome, threat of premature birth, convulsions in preeclampsia, eclampsia.

Poisoning by heavy metal salts (mercury, arsenic, tetraethyllead, barium).

ICD codes

Dosage Regimen

Solution

Intravenously, slowly.

Doses are adjusted according to the therapeutic effect and the concentration of magnesium ions in the blood serum.

Preeclampsia and eclampsia. The dose is set individually depending on the clinical situation. Loading dose 2 – 4 g over 5 – 20 minutes (infusion). Maintenance dose 1 – 2 g per hour.

Uterine tetany. Loading dose 4 g over 20 minutes (infusion). Maintenance dose initially 1-2 g per hour, later 1 g per hour (can be administered by drip for 24-72 hours).

Hypomagnesemia

In newborns, the daily dose is 0.2-0.8 mg/kg intravenously slowly.

In adults

Mild. Cormagnesin^® is used parenterally if the oral route of administration of magnesium preparations is impossible or inappropriate (due to nausea, vomiting, impaired gastric resorption, etc.).

Severe. The initial dose is 5 g. The dose is infused in 1 liter of infusion solution and administered intravenously slowly. The dose is selected depending on the concentration of the drug in the blood serum.

Prevention of hypomagnesemia in patients receiving only parenteral nutrition. If there is no magnesium in the nutrient solutions, it is added additionally. The daily dose is 1.5-4 g. Usually, 1 g of magnesium sulphate is added to 1 liter of parenteral nutrition solution. The maximum daily dose of magnesium sulphate for adults is 40 g. For hypertensive crises, 1-4 g of Cormagnesin^® solution is administered intravenously slowly.

For relief of arrhythmias, 1-2 g is administered intravenously over about 5 minutes, repeated administration is possible.

The doses of the drug Cormagnesin^® are indicated in grams.

They correspond to the amount of solution: 1 g – 5 ml (200 mg/ml); 2 g – 10 ml (200 mg/ml); 3 g – 15 ml (200 mg/ml); 4 g – 20 ml (200 mg/ml); 5 g – 25 ml (200 mg/ml); 10 g -50 ml (200 mg/ml); 15 g – 75 ml (200 mg/ml); 20 g – 100 ml (200 mg/ml); 30 g – 150 ml (200 mg/ml ); 40 g – 200 ml (200 mg/ml).

Cormagnesin^® solution in ampoules is diluted with injection solutions: 0.9% sodium chloride or 5% dextrose (glucose).

Adverse Reactions

Early signs and symptoms of hypermagnesemia bradycardia, diplopia, sudden flushing of the face, headache, dizziness, decreased blood pressure, nausea, shortness of breath, slurred speech, vomiting, asthenia.

Signs of hypermagnesemia (in order of increasing serum magnesium concentration): decrease in deep tendon reflexes (2-3.5 mmol/L), prolongation of the PQ interval and widening of the QRS complex on ECG (2.5-5 mmol/L), loss of deep tendon reflexes (4-5 mmol/L), depression of the respiratory center (5-6.5 mmol/L), impaired cardiac conduction (7.5 mmol/L), cardiac arrest (12.5 mmol/L).

When taken orally nausea, vomiting, diarrhea, exacerbation of inflammatory gastrointestinal diseases, electrolyte imbalance (increased fatigue, asthenia, confusion, arrhythmia, convulsions), flatulence, abdominal pain of a spasmodic nature, thirst, signs of hypermagnesemia in the presence of renal failure.

With IV administration slowing of respiratory rate, shortness of breath; acute circulatory failure; weakening of reflexes; hyperemia; pronounced decrease in blood pressure; hypothermia; weakening of muscle tone; uterine atony; hyperhidrosis; anxiety; pronounced sedation; polyuria; decreased heart rate; ECG changes. Magnesium sulphate reduces the excitability of the respiratory center, high doses with parenteral administration can cause paralysis of the respiratory center.

Contraindications

Hypersensitivity to magnesium sulphate; severe chronic renal failure.

For oral administration: appendicitis, rectal bleeding (including undiagnosed), intestinal obstruction, dehydration, hypermagnesemia; pregnancy, breastfeeding period; children under 18 years of age.

With caution cardiac conduction disorders, heart failure, chronic renal failure.

For parenteral administration: severe arterial hypotension, depression of the respiratory center, severe bradycardia, AV block I-III degree; intrapartum period (within 2 hours of delivery); conditions associated with calcium deficiency.

With caution myasthenia gravis; chronic renal failure (creatinine clearance 20-60 ml/min); respiratory diseases; acute inflammatory gastrointestinal diseases; elderly age, pregnancy, breastfeeding period, age under 18 years.

Use in Pregnancy and Lactation

The use of magnesium sulphate orally is contraindicated during pregnancy. Parenteral use during pregnancy is possible only as prescribed by a doctor if the intended benefit to the mother outweighs the potential risk to the fetus; its use is contraindicated in the intrapartum period (within 2 hours of delivery).

If use during lactation is necessary, breastfeeding should be discontinued.

Use in Renal Impairment

Contraindicated in severe chronic renal failure. Use with caution orally or parenterally in chronic renal failure.

Pediatric Use

Use in children is possible according to indications, in age-appropriate recommended doses and dosage forms. It is necessary to strictly follow the instructions in the magnesium sulphate drug leaflets regarding contraindications for the use of specific dosage forms of magnesium sulphate in children of different ages.

Geriatric Use

Use parenterally with caution in elderly patients; a reduced dose should usually be used in this category of patients due to reduced renal function.

Special Precautions

Use with caution orally or parenterally in cases of heart block, myocardial damage, chronic renal failure, respiratory diseases, acute inflammatory gastrointestinal diseases, pregnancy.

Magnesium sulphate should be used cautiously in elderly patients. A reduced dose should usually be used in this category of patients due to reduced renal function.

Magnesium sulphate can be used to relieve status epilepticus (as part of complex treatment).

Overdose causes depression of the CNS. Calcium preparations – calcium chloride or calcium gluconate – are used as an antidote for magnesium sulphate overdose.

The use of magnesium sulphate may distort the results of radiological studies that use technetium.

Influence on the ability to drive vehicles and mechanisms

During treatment, patients should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (risk of diplopia, dizziness, headache).

Drug Interactions

Magnesium sulphate enhances the effect of other drugs that depress the CNS.

With parenteral use of magnesium sulphate and simultaneous use of peripheral muscle relaxants, the effects of peripheral muscle relaxants are enhanced.

A case of respiratory arrest has been described with the use of gentamicin in an infant with elevated plasma magnesium concentration during therapy with magnesium sulphate.

When used concomitantly with nifedipine, pronounced muscle weakness is possible.

It reduces the effectiveness of oral anticoagulants (including coumarin derivatives or indandione derivatives), cardiac glycosides, phenothiazines (especially chlorpromazine). It reduces the absorption of ciprofloxacin, etidronic acid, and weakens the action of streptomycin and tobramycin.

With concomitant use of magnesium sulphate for parenteral administration with other vasodilators, an enhancement of the hypotensive effect is possible.

Barbiturates, narcotic analgesics, and antihypertensive drugs increase the likelihood of depression of the respiratory center.

It impairs the absorption of tetracycline antibiotics and weakens the action of streptomycin and tobramycin. Calcium salts reduce the effect of magnesium sulphate.

If the magnesium ion content is above 10 mmol/ml in mixtures for total parenteral nutrition, separation of fat emulsions is possible.

Calcium preparations – calcium chloride or calcium gluconate – are used as an antidote for magnesium sulphate overdose.

Pharmaceutically incompatible (precipitate forms) with calcium preparations, ethanol (in high concentrations), carbonates, bicarbonates and phosphates of alkali metals, salts of arsenic acid, barium, strontium, clindamycin phosphate, hydrocortisone sodium succinate, polymyxin B sulphate, procaine hydrochloride, salicylates and tartrates.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.